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Occludin regulates γδ intraepithelial lymphocyte migration in vivo
Author(s) -
Edelblum Karen L,
Marchiando Amanda M,
Sperling Anne I,
Turner Jerrold R
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1121.2
Subject(s) - occludin , intraepithelial lymphocyte , microbiology and biotechnology , chemistry , tight junction , microfold cell , immunology , biology , immune system
Intraepithelial lymphocytes (IELs) expressing the γδ T cell receptor promote mucosal homeostasis. To define the mechanisms by which they interact with enterocytes, jejunum of mice expressing GFP γδ T cells was imaged in vivo . At steady‐state, 32% of γδT cells are intraepithelial, but they exit this compartment with an average dwell time of ~6 min. This dynamic behavior allows each epithelial cell to interact with 3.5±0.2 γδIELs/hr. The tight junction protein occludin is expressed by γδIELs and concentrated at sites of γδIEL/epithelial contact. To assess the function of γδIEL occludin, mixed chimeras were generated by engrafting γδ T cell‐deficient marrow (80%), combined with either wildtype GFPγδ or occludin KO GFPγδ marrow (20%), into irradiated hosts. Occludin KO γδ T cells migrated into the epithelium inefficiently (13% vs. 41% for wildtype), and occludin KO γδIELs that crossed the basement membrane often remained subepithelial and rarely entered the lateral intercellular space. Occludin KO γδ T cells also migrated more slowly and interacted with fewer epithelial cells than wildtype γδ T cells (max speed 4.0±0.1 μm/min vs. 4.7±0.1μm/min, respectively; 1 epithelial cell/0.7±0.1 occludin KO γδIELs vs. 4.2±0.4 wildtype γδIELs/hr). Taken together, these data demonstrate that occludin is a critical regulator of γδIEL migration within the epithelium. Funding: NIH DK084859 (KLE), R01DK068271, R01DK061931 (JRT)